Four year follow-up shows Kaletra to be safe, effective, durable

Michael Carter
Published: 05 April 2004

Lopinavir/ritonavir (KaletraTM) has a potent and durable anti-HIV effect when used in combination with d4T and 3TC, and a good side-effect profile, according to a long-term safety study published in the March 25th edition of AIDS. The study investigators conclude that these results support the use of Kaletra in first-line HAART regimens.

Investigators looked at four-year HIV suppression and adverse events in 100 individuals who participated in an early clinical trial of the safety and effectiveness of Kaletra when used as part of a HAART regimen in HIV-positive, treatment-naïve individuals.

At baseline, individuals had a mean HIV viral load of 80,000 copies/ml and a mean CD4 cell count of 338 cells/mm3. The mean age was 35 years, 96% of individuals were men, just under two thirds were Caucasian, 29% were African-American and 6% were Hispanic. Initially, patients were randomised to receive one of three blinded doses of lopinavir/ritonavir in combination with 3TC and d4T. At 48 weeks all patients were prescribed a twice-daily lopinavir/ritonavir dose of 400/100mg with 3TC and d4T, after data showed that this achieved maximum plasma levels of the protease inhibitor and had the most favourable side-effect profile. This dose was licensed as Kaletra.

A total of 28 patients withdrew from the study, ten for safety reasons, nine were lost to follow-up, and nine for other reasons.

Of the 72 individuals remaining on Kaletra at week 204, 71 had a viral load below 400 copies/ml and 70 had a viral load below 50 copies/ml. This meant that in on-treatment analysis, 97% of patients had a viral load below 50 copies/ml after four years, with the more rigorous intent-to-treat analysis indicating that 70% of individuals had HIV suppression below 50 copies/ml at week 204.

Virological failure was observed in 15 patients. Eight of these patients withdrew from the study, but the other seven individuals regained viral control and had a viral load below 50 copies/ml at week 204. No individual developed resistance to protease inhibitors, although three patients showed the M184V mutation, which confers resistance to 3TC.

The mean CD4 cell count from baseline was 440 cells/mm3, and at week 204, 65 (90%) of the 72 individuals remaining on the study had a CD4 cell count above 350 cells/mm3. The remaining seven patients had a median CD4 cell count of 204 cells/mm3 at week 204, and all seven had achieved an increase in their baseline CD4 cell count of at least 100 cells/mm3.

Of the ten patients who withdrew from the study because of side-effects, seven were thought by their doctors to have experienced an adverse event which was possibly related to the study medication, including one patient who died of a heart attack, two individuals with asymptomatic elevated liver function, one patient with diarrhoea, and one individual with elevated cholesterol.

The most commonly reported mild-to-moderate side-effects were diarrhoea (27%), nausea (16%), and abdominal pain (10%). At week 204, two patients still reported diarrhoea.

Body fat changes were observed in a total of 25 patients at week 204, including 14 with fat loss, five with fat pain, and six with both. The median time to the onset of body fat changes was 120 weeks.

At week 204, one patient had grade 3 elevated cholesterol, and four patients had grade 3 elevated triglycerides. A total of 19 individuals were prescribed lipid-lowering drugs during the course of the study, and 15 remained on them at week 204.

Grade 3 ALT levels were observed in a total of eleven patients. This included 45% of individuals with hepatitis B or C infection (5/11) compared to 7% of patients who were not coinfected with these liver viruses.

The investigators conclude “this long-term follow-up study of [Kaletra] treated patients demonstrated durable HIV suppression and substantial increases in CD4 cell counts over four years. These data support the use of [Kaletra] in the initial treatment of HIV infection.”

Further information on this website

Lopinaivr - overview


Hicks C et al. Long-term safety and durable antiretroviral activity of lopinavir/ritonavir in treatment-naïve patients: 4 year follow-up study. AIDS 18: 775 – 779, 2004.

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